Dietary Methionine Enhances Portal Appearance of Guanidinoacetate and Synthesis of Creatine in Yucatan Miniature Piglets

J Nutr. 2024 Mar 26:S0022-3166(24)00166-4. doi: 10.1016/j.tjnut.2024.03.017. Online ahead of print.

Abstract

Background: Creatine plays a significant role in energy metabolism and positively impacts anaerobic energy capacity, muscle mass, and physical performance. Endogenous creatine synthesis requires guanidinoacetic acid (GAA) and methionine. GAA can be an alternative to creatine supplements and has been tested as a beneficial feed additive in the animal industry. When pigs are fed GAA with excess methionine, creatine is synthesized without feedback regulation. In contrast, when dietary methionine is limited, creatine synthesis is limited, yet, GAA does not accumulate in plasma, urine, or liver.

Objective: We hypothesized that portal GAA appearance requires adequate dietary methionine.

Methods: Yucatan miniature piglets (17-21 d old; n = 20) were given a 4 h duodenal infusion of complete elemental diets with supplemental GAA plus 1 of 4 methionine concentrations representing either 20%, 80%, 140%, or 200% of the dietary methionine requirement. Arterial and portal blood metabolites were measured along with blood flow to determine mass balance across the gut. [3H-methyl] methionine was infused to measure the methionine incorporation rate into creatine.

Results: GAA balance across the gut was highest in the 200% methionine group, indicating excess dietary methionine enhanced GAA absorption. Creatine synthesis in the liver and jejunum was higher with higher concentrations of methionine, emphasizing that the transmethylation of GAA to creatine depends on sufficient dietary methionine. Hepatic GAA concentration was higher in the 20% methionine group, suggesting low dietary methionine limited GAA conversion to creatine, which led to GAA accumulation in the liver.

Conclusions: GAA absorption and conversion to creatine require a sufficient amount of methionine, and the supplementation strategies should accommodate this interaction.

Keywords: GAA absorption; GAA supplementation; Methionine; creatine; piglets.